Uptake of Sodium Valproate and Effects on GABA Transport in Astroglial Primary Culture

1989 ◽  
Vol 16 (3) ◽  
pp. 244-247
Author(s):  
Michael Nilsson ◽  
Elisabeth Hansson ◽  
Lars Rönnbäck
Keyword(s):  
Valproic Acid ◽  
Cerebral Cortex ◽  
Sodium Valproate ◽  
Gaba Uptake ◽  
Newborn Rat ◽  
Gaba Transport ◽  
High Affinity ◽  
Major Factors ◽  
The Brain ◽  
Anticonvulsant Effects

The sodium salt of valproic acid (VPA) is an antiepileptic drug, which is effective in the treatment of several types of epilepsy. The drug has been postulated to exert its anticonvulsant effects by interaction with GABA-ergic systems in the brain. Results show a high-affinity uptake for sodium valproate in primary astroglial cultures from newborn rat cerebral cortex, with the kinetic parameters Km and Vmax not significantly different from those observed for GABA. This uptake was shown to interact with astroglial GABA transport in culture, with an increased Km value for GABA uptake. Since failure in GABA-ergic systems is postulated to be one of the major factors in the aetiology of epilepsy, it is interesting to note that the transport system for GABA in astrocytes is affected by sodium valproate.

scholarly journals Inhibition of high-affinity gamma-aminobutyric acid uptake in primary astrocyte cultures by phorbol esters and phospholipase C

1991 ◽  
Vol 275 (2) ◽  
pp. 435-439 ◽  
Author(s):  
J Gomeza ◽  
M Casado ◽  
C Gimenez ◽  
C Aragon
Keyword(s):  
Phospholipase C ◽  
Glial Cells ◽  
Kinase Inhibitor ◽  
Primary Cultures ◽  
Aminobutyric Acid ◽  
Gaba Uptake ◽  
Acid Uptake ◽  
Gamma Aminobutyric Acid ◽  
Gaba Transport ◽  
High Affinity

The effects of phorbol 12-myristate 13-acetate (PMA), a potent activator of protein kinase C (PKC), on high-affinity Na(+)-dependent gamma-aminobutyric acid (GABA) uptake were investigated in primary cultures of neurons and glial cells from rat brain cortex. Incubation of glial cells with PMA led to concentration- and time-dependent decreases in the GABA transport in glial cells. This effect could be completely suppressed by addition of the PKC inhibitor H7. The PMA effects could be mimicked by oleoylacetylglycerol, the diacylglycerol kinase inhibitor R59022 and exogenous phospholipase C. Treatment with PMA did not affect GABA transport in neuronal cells.

The beneficial effects of l-cysteine on brain antioxidants of rats affected by sodium valproate

2017 ◽  
Vol 36 (11) ◽  
pp. 1212-1221 ◽  
Author(s):  
RZ Hamza ◽  
NS El-Shenawy
Keyword(s):  
Oxidative Stress ◽  
Cerebral Cortex ◽  
Protective Effect ◽  
Brain Tissue ◽  
Sodium Valproate ◽  
Histopathological Examination ◽  
Control Group ◽  
High Dose ◽  
Beneficial Effects ◽  
The Brain

Oxidative stress caused by sodium valproate (SV) is known to play a key role in the pathogenesis of brain tissue. The present study was designed to evaluate the protective effect of l-cysteine (LC) on the antioxidants of brain tissue of rats. The animals were divided into six groups: control group 1 was treated with saline as vehicle, groups 2 and 3 were treated with low and high doses of SV (100 and 500 mg/kg, respectively), group 4 was treated with LC (100 mg/kg), and groups 5 and 6 were treated with low-dose SV + LC and high-dose SV + LC, respectively. All the groups were treated orally by gastric tube for 30 successive days. Some antioxidant parameters were determined. Brain tissue (cerebral cortex) of SV-treated animals showed an increase in lipid peroxidation (LPO) and reduction in activity of enzymatic antioxidant and total antioxidant levels. Histopathological examination of cerebral cortex of SV rats showed astrocytic swelling, inflammation, and necrosis. After 4 weeks of the combination treatment of SV and LC daily, results showed significant improvement in the activity of cathepsin marker enzymes and restored the structure of the brain. LC was able to ameliorate oxidative stress deficits observed in SV rats. LC decreased LPO level and was also able to restore the activity of antioxidant enzymes as well as structural deficits observed in the brain of SV animals. The protective effect of LC in SV-treated rats is mediated through attenuation of oxidative stress, suggesting a therapeutic role for LC in individuals treated with SV.

scholarly journals Investigation of the anticonvulsant and remyelinating potential of dexketoprofen on a rat model of primary generalized seizures

2020 ◽  
Vol 12 (4) ◽  
pp. 84-90
Author(s):  
O. A. Gromova ◽  
V. I. Demidov ◽  
A. G. Kalacheva ◽  
I. Yu. Torshin ◽  
T. R. Grishina ◽  
...  
Keyword(s):  
Rat Brain ◽  
Sodium Valproate ◽  
Rat Model ◽  
Histopathological Examination ◽  
Neuroprotective Effect ◽  
Albino Rats ◽  
Generalized Seizures ◽  
Seizure Model ◽  
The Brain ◽  
Anticonvulsant Effects

Objective: to investigate the effect of dexketoprofen on the severity of seizures on a rat model of primary generalized seizures caused by thiosemicarbazide; to evaluate the neuroprotective effect of the drug.Material and methods. The investigation was conducted on 72 male albino rats weighing 200–300 g. The animals were given dexketoprofen and/or comparison drugs (gabapentin, sodium valproate) for 5 days, after which the seizure model was reproduced. The effects of the drugs were evaluated from a set of neurological tests and the results of a histopathological examination of the brain.Results and discussion. Dexketoprofen reduced the severity, duration, and number of primary generalized seizures and potentiated the anticonvulsant effects of gabapentin and sodium valproate. Histopathological and morphometric examinations of the rat brain showed that dexketoprofen inhibited the formation of irreversible neuronal changes (27.2%; control, 55.7%), by transferring them into reversible changes (47.7%; control, 21.8%).Conclusion. The investigation made it possible to conclude that dexketoprofen had a moderate neuroprotective effect neurologically and morphometrically verified.

scholarly journals Bradykinin Receptors of Cerebral Microvessels Stimulate Phosphoinositide Turnover

1991 ◽  
Vol 11 (4) ◽  
pp. 557-566 ◽  
Author(s):  
Parvin Homayoun ◽  
Sami I. Harik
Keyword(s):  
Cerebral Cortex ◽  
Ligand Binding ◽  
Specific Binding ◽  
Receptor Site ◽  
Cerebral Microvessels ◽  
High Affinity ◽  
Phosphoinositide Turnover ◽  
Brain Microvessels ◽  
Brain Microcirculation ◽  
The Brain

We examined by ligand binding methods whether bradykinin (BK) receptors exist in rat and pig cerebral microvessels, and in the cerebral cortex from which the microvessels were isolated. We found a high-affinity and saturable BK receptor site in both rat and pig cerebral microvessels, but not in their cerebral cortex. The maximal density of binding and the dissociation constant were 8.0 ± 4.1 and 6.8 ± 1.5 fmol/mg of protein and 47 ± 24 and 150 ± 8 p M (mean ± SD) in cerebral microvessels of the pig and rat, respectively. The high-affinity specific binding of BK was effectively displaced by des-Arg0[Hyp3-Thi5–8,D-Phe7]BK, a specific B2 receptor antagonist, but not by des-Arg9[Leu8]BK, a specific B1 antagonist. We also demonstrated that BK increases phosphatidylinositol hydrolysis in cerebral microvessels of the rat and pig. This effect was also blocked by the B2, but not by the B1, antagonist. Increased phosphatidylinositol hydrolysis was manifested by a rapid transient increase in inositol trisphosphate and the later slow accumulation of inositol bisphosphate and inositol monophosphate. Preincubation of microvessels with phorbol ester, stable GTP analogs, pertussis toxin, or in Ca2+-free buffer did not influence BK activation of phosphatidylinositol hydrolysis. These results demonstrate the existence of BK receptors of the B2 subtype in brain microvessels, which may play an important role in modulation of the brain microcirculation, probably via increased phosphoinositide turnover.

Relationship between levels and uptake of serotonin and high affinity [3H]imipramine recognition sites in the rat brain

1985 ◽  
Vol 63 (10) ◽  
pp. 1239-1244 ◽  
Author(s):  
Pavel D. Hrdina ◽  
Bruce A. Pappas ◽  
David C. S. Roberts ◽  
Robert J. Bialik ◽  
Cathrine L. Ryan
Keyword(s):  
Cerebral Cortex ◽  
Brain Regions ◽  
Serotonin Uptake ◽  
Noradrenaline Content ◽  
Serotonergic Neurons ◽  
High Affinity ◽  
Recognition Sites ◽  
Imipramine Binding ◽  
6 Hydroxydopamine ◽  
The Brain

High affinity [3H]imipramine binding, endogenous levels of serotonin and noradrenaline, and serotonin uptake were determined in brain regions of rats with selective destruction of serotonergic neurons by 5,7-dihydroxytryptamine (5,7-DHT), of adrenergic neurons by 6-hydroxydopamine (6-OHDA), and of rats treated with reserpine. Neonatal treatment with 5,7-DHT resulted in a significant decrease of both serotonin levels and density (Bmax) of high affinity [3H]imipramine binding sites in the hippocampus. In contrast, an elevation of serotonin levels and an increase in Bmax of [3H]imipramine binding were noted in the pons–medulla region. No changes were observed in the noradrenaline content in either of these regions. Intracerebral 6-OHDA lesion produced a drastic suppression of noradrenaline levels in cerebral cortex but failed to alter the binding affinity (KD) or density (Brnax) of [3H]imipramine recognition sites. A single injection of reserpine (2.5 mg/kg) resulted in marked depletion of both serotonin (by 57%) and noradrenaline (by 86%) content and serotonin uptake (by 87%) in the cerebral cortex but had no significant influence of the parameters of high affinity [3H]imipramine binding in this brain region. The results suggest that high affinity [3H]imipramine binding in the brain is directly related to the integrity of serotonergic neurons but not to the magnitude of the uptake or the endogenous levels of the transmitter, and is not affected by damage to noradrenergic neurons or by low levels of noradrenaline.

Glucuronyl 3-sulfate occurs exclusively on distal unmyelinated terminals of selected sensory neurons in the peripheral nervous system

1995 ◽  
Vol 53 ◽  
pp. 958-959
Author(s):  
S.S. Spicer ◽  
B.A. Schulte
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Cerebral Cortex ◽  
Peripheral Nervous System ◽  
Sensory Neurons ◽  
Sensory Nerves ◽  
Tissue Antigens ◽  
The Central Nervous System ◽  
The Brain ◽  
Leu 7

Generation of monoclonal antibodies (MAbs) against tissue antigens has yielded several (VC1.1, HNK- 1, L2, 4F4 and anti-leu 7) which recognize the unique sugar epitope, glucuronyl 3-sulfate (Glc A3- SO4). In the central nervous system, these MAbs have demonstrated Glc A3-SO4 at the surface of neurons in the cerebral cortex, the cerebellum, the retina and other widespread regions of the brain.Here we describe the distribution of Glc A3-SO4 in the peripheral nervous system as determined by immunostaining with a MAb (VC 1.1) developed against antigen in the cat visual cortex. Outside the central nervous system, immunoreactivity was observed only in peripheral terminals of selected sensory nerves conducting transduction signals for touch, hearing, balance and taste. On the glassy membrane of the sinus hair in murine nasal skin, just deep to the ringwurt, VC 1.1 delineated an intensely stained, plaque-like area (Fig. 1). This previously unrecognized structure of the nasal vibrissae presumably serves as a tactile end organ and to our knowledge is not demonstrable by means other than its selective immunopositivity with VC1.1 and its appearance as a densely fibrillar area in H&E stained sections.

Neurotransmitter systems of female mouse brain during growth of malignant melanoma modeled on the background of chronic pain

2018 ◽  
pp. 49-55
Author(s):  
О.И. Кит ◽  
И.М. Котиева ◽  
Е.М. Франциянц ◽  
И.В. Каплиева ◽  
Л.К. Трепитаки ◽  
...  
Keyword(s):  
Chronic Pain ◽  
Cerebral Cortex ◽  
Malignant Melanoma ◽  
Sciatic Nerve ◽  
Female Mouse ◽  
Combined Effects ◽  
Malignant Growth ◽  
Course Of Disease ◽  
The Brain ◽  
Melanoma Growth

Известно, что биогенные амины (БА) участвуют в злокачественном росте, их уровень изменяется в ЦНС при болевом воздействии, однако исследований о сочетанном влиянии хронической боли (ХБ) и онкопатологии на динамику БА в головном мозге не проводилось. Цель: изучить особенности баланса БА в коре головного мозга в динамике роста меланомы, воспроизведенной на фоне ХБ. Материалы и методы. Работа выполнена на 64 мышах-самках, весом 21-22 г. Животным основной группы меланому В16/F10 перевивали под кожу спины через 2 недели после перевязки седалищных нервов. Группой сравнения служили мыши с меланомой без боли. Уровни БА: адреналина, норадреналина, дофамина (ДА), серотонина (5-НТ), гистамина, а также 5-ОИУК определяли методом иммуноферментного анализа. Результаты. У мышей с ХБ уменьшается содержание большинства БА, однако уровень ДА не изменяется. Метаболизм 5-НТ происходит с участием МАО. Развитие меланомы сопровождается увеличением содержания ДА и 5-НТ, тогда как МАО - ингибируется. Направленность сдвигов БА при развитии меланомы на фоне ХБ оказалась практически такой же, как и без неё. В то же время ХБ ограничивает накопление 5-НТ в коре мозга при меланоме, что сопровождается более агрессивным её течением. Выводы. ХБ ограничивает включение стресс-лимитирующих механизмов в головном мозге при развитии меланомы у мышей, что приводит к более агрессивному течению злокачественного процесса. Biogenic amines (BA) are known to be involved in malignant growth, and their CNS levels change in pain; however, there are no studies of combined effects of chronic pain (CP) and cancer on BA dynamics in the brain. Aim: To study features of BA balance in the cerebral cortex during melanoma growth associated with CP. Material and methods. The study included 64 female mice weighing 21-22 g. In the main groups, B16/F10 melanoma was transplanted under the skin of the back two weeks following sciatic nerve ligation. Mice with melanoma without pain were used as the control. Concentrations of BA: adrenaline, noradrenaline, dopamine (DA), serotonin (5-HT), histamine and 5-HIAA were measured with ELISA. Results. Concentrations of BAs decreased in mice with CP although DA levels did not change. 5-HT metabolism involved MAO. The development of melanoma was accompanied by increases in DA and 5-HT whereas MAO was inhibited. The direction of BA changes during the development of melanoma was the same with and without CP. At the same time, CP with melanoma limited accumulation of 5-HT in the cerebral cortex, which resulted in even more aggressive course of cancer. Conclusion. CP restricted the activation of cerebral stress-limiting mechanisms during the development of melanoma in mice, which resulted in a more aggressive course of disease.

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